Robust joint analysis allowing for model uncertainty in two-stage genetic association studies

doi:10.1186/1471-2105-12-9

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	Robust joint analysis allowing for model uncertainty in two-stage genetic association studies
	Pan, Dongdong 1,2; Li, Qizhai1 ; Jiang, Ningning 1; Liu, Aiyi 3; Yu, Kai 4
	2011-01-07
发表期刊	BMC BIOINFORMATICS
ISSN	1471-2105
卷号	12 页码:7
摘要	Background: The cost efficient two-stage design is often used in genome-wide association studies (GWASs) in searching for genetic loci underlying the susceptibility for complex diseases. Replication- based analysis, which considers data from each stage separately, often suffers from loss of efficiency. Joint test that combines data from both stages has been proposed and widely used to improve efficiency. However, existing joint analyses are based on test statistics derived under an assumed genetic model, and thus might not have robust performance when the assumed genetic model is not appropriate. Results: In this paper, we propose joint analyses based on two robust tests, MERT and MAX3, for GWASs under a two-stage design. We developed computationally efficient procedures and formulas for significant level evaluation and power calculation. The performances of the proposed approaches are investigated through the extensive simulation studies and a real example. Numerical results show that the joint analysis based on the MAX3 test statistic has the best overall performance. Conclusions: MAX3 joint analysis is the most robust procedure among the considered joint analyses, and we recommend using it in a two-stage genome-wide association study.
DOI	10.1186/1471-2105-12-9
语种	英语
资助项目	National Young Science Foundation of China[10901155]
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Mathematical & Computational Biology
WOS类目	Biochemical Research Methods ; Biotechnology & Applied Microbiology ; Mathematical & Computational Biology
WOS记录号	WOS:000286598800001
出版者	BIOMED CENTRAL LTD
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/185
专题	系统科学研究所
通讯作者	Li, Qizhai
作者单位	1.Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China 2.Yunnan Univ, Dept Stat, Kunming 650091, Peoples R China 3.Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA 4.NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
推荐引用方式 GB/T 7714	Pan, Dongdong,Li, Qizhai,Jiang, Ningning,et al. Robust joint analysis allowing for model uncertainty in two-stage genetic association studies[J]. BMC BIOINFORMATICS,2011,12:7.
APA	Pan, Dongdong,Li, Qizhai,Jiang, Ningning,Liu, Aiyi,&Yu, Kai.(2011).Robust joint analysis allowing for model uncertainty in two-stage genetic association studies.BMC BIOINFORMATICS,12,7.
MLA	Pan, Dongdong,et al."Robust joint analysis allowing for model uncertainty in two-stage genetic association studies".BMC BIOINFORMATICS 12(2011):7.